Co-culture with lung cancer A549 cells promotes the proliferation and migration of mesenchymal stem cells derived from bone marrow

Abstract

The initiation and progression of various types of tumors, such as lung neoplasms, are driven by a population of cells with stem cell properties and their microenvironment. Bone marrow mesenchymal stem cells (BM-MSCs) in long-term in vitro culture may exhibit spontaneous changes in stem cell biological properties, including malignant transformations; however, the molecular mechanisms of this have not been fully elucidated. In the present study, a BM-MSC and lung cancer A549 cell co-culture system was utilized to investigate how the tumor microenvironment may spontaneously change the proliferation, migration and differentiation of BM-MSCs. It was demonstrated that the lung cancer A549 microenvironment is able to induce changes in the cell morphology, proliferation, karyotype, cytoskeleton and migration ability of BM-MSCs in vitro. Compared with the control group BM-MSCs, the expression of Ras, phosphorylated-extracellular regulated protein kinases, nuclear factor-κB, P62 and B-cell lymphoma 2 (Bcl-2) proteins in groups of co-cultured BM-MSCs increased significantly (P<0.05) and the expression of P53, Bcl-2 associated X protein and caspase-3 protein decreased significantly (P<0.05). The mechanisms responsible for the changes observed in BM-MSCs may be related to abnormal expression of related genes in the ERK signaling pathway.

RETRACTED ARTICLE: Exosomes from glioma cells induce a tumor-like phenotype in mesenchymal stem cells by activating glycolysis

“…However, exosomes produced by tumor cells are capable of influencing MSCs [28, 29]. MSCs are reportedly intimately associated with tumor cells in the tumor microenvironment; indeed, co-culture with lung cancer A549 cells promoted the proliferation and migration of hBMSCs, likely by modulating the expression of genes related to the ERK signaling pathway [30]. Furthermore, C6 glioma-conditioned medium induced a tumor-like phenotype in MSCs, possibly in a manner involving the S100B/RAGE pathway [31].…”

The Effects of Astragalus Polysaccharide on Bone Marrow-Derived Mesenchymal Stem Cell Proliferation and Morphology Induced by A549 Lung Cancer Cells

“…The present in vitro study included four groups of cells, A549 lung cancer cells, untreated bone marrow-derived MSCs, untreated bone marrow-derived MSCs co-cultured with A549 cells (Co-BMSCs), and co-cultured bone marrow-derived MSCs and A549 cells treated with 50 μg/ml of Astragalus polysaccharide (APS) (Co-BMSCs + APS). In a previous study, we reported that Co-BMSCs showed a high rate of proliferation and abnormal changes in morphology, which are findings supported by those of the present study [32]. Previous studies have shown that lung tumor exosomes initiated changes in long non-coding RNA (lncRNA) [15], and induced a pro-inflammatory phenotype of MSCs via the nuclear factor-kappaB (NF-κB) and Toll-like Receptor (TLR) signaling pathways [14].…”

MRI detection of the malignant transformation of stem cells through reporter gene expression driven by a tumor-specific promoter

“…It has been reported that MSCs can be recruited to tumors and participate in the formation of the tumor stroma [ 43 – 47 ]. Recent studies have shown that MSCs can undergo malignant transformation when they are cultured for a long period of time or in a tumor-like environment, although the underlying mechanism remains unknown [ 10 , 30 , 48 , 49 ]. In this study, we induced MSCs to undergo malignant transformation by indirectly coculturing them with C6 glioma cells.…”